Angiotensin II is a powerful vasoconstrictor and its actions to increase vascular tone are mediated by AT1 receptors. The absence of extra-renal AT1A receptors reduces blood pressure by ~20mm Hg, demonstrating a non-redundant contribution of extra-renal AT1A receptors to chronic regulation of blood pressure. We hypothesize that the effects of AT1A receptors in vascular smooth muscle cells account for a significant portion of blood pressure control mediated by cell lineages outside the kidney. To test their capacity to affect blood pressure regulation, we will delete AT1A receptors specifically in vascular smooth muscle cells. Along with effects on blood pressure, we will also determine the consequences of this genetic manipulation on renal blood flow. Because renal hemodynamic actions of AT1A receptors could impact sodium excretion and thereby affect blood pressure, we will carry out kidney cross-transplants in order to separate the systemic and renal vascular actions of AT1A receptors. As AT1B receptors have modest effects to regulate vascular tone, we will also delete AT1A receptors from vascular smooth muscle cells on an AT1B receptor-deficient background.